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Re: DTaP package Insert

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Sheri, what is erythema??? It's listed as one of the (many) side effects.

At 10:48 AM 12/16/01 +0000, you wrote:

>

>Here is the package insert for DTaP. They can all be gotten on

><http://www.pdr.net>www.pdr.net

>

>SIDS!

>

>-Dawn

>

> PDR® entry for

>Tripedia (Pasteur Merieux Connaught)

>

>

>

>CAUTION: Federal (USA) law prohibits dispensing without prescription.

>

>

>

>DESCRIPTION

>

>

>Tripedia®, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine

>Adsorbed (DTaP), for intramuscular use, is a sterile preparation of

>diphtheria and tetanus toxoids adsorbed, with acellular pertussis vaccine

>in an isotonic sodium chloride solution containing thimerosal as a

>preservative and sodium phosphate to control pH. After shaking, the vaccine

>is a homogeneous white suspension. Tripedia® vaccine is distributed by

>Connaught Laboratories, Inc. (CLI).

>

>The acellular pertussis vaccine components are isolated from culture fluids

>of Phase 1 Bordetella pertussis grown in a modified Stainer-Scholte medium.

>1 After purification by salt precipitation, ultracentrifugation, and

>ultrafiltration, preparations containing varying amounts of both pertussis

>toxin (PT) and filamentous hemagglutinin (FHA) are combined to obtain a 1:1

>ratio and treated with formaldehyde to inactivate PT. Thimerosal (mercury

>derivative) 1:10,000 is added as a preservative.

>

>Corynebacterium diphtheriae cultures are grown in a modified Mueller and

> medium. 2 Clostridium tetani cultures are grown in a peptone-based

>medium. Both toxins are detoxified with formaldehyde. The detoxified

>materials are then separately purified by serial ammonium sulfate

>fractionation and diafiltration.

>

>The toxoids are adsorbed using aluminum potassium sulfate (alum). The

>adsorbed diphtheria and tetanus toxoids are combined with acellular

>pertussis concentrate, and diluted to a final volume using sterile

>phosphate-buffered physiological saline. Thimerosal (mercury derivative)

>1:10,000 is added as a preservative. Each 0.5 mL dose contains, by assay,

>not more than 0.170 mg of aluminum and not more than 100 µg (0.02%) of

>residual formaldehyde. The vaccine contains gelatin and polysorbate 80

>(Tween-80) which are used in the production of the pertussis concentrate.

>

>Each 0.5 mL dose is formulated to contain 6.7 Lf of diphtheria toxoid and 5

>Lf of tetanus toxoid (both toxoids induce at least 2 units of antitoxin per

>mL in the guinea pig potency test), and 46.8 µg of pertussis antigens. This

>is represented in the final vaccine as approximately 23.4 µg of inactivated

>PT (also referred to as lymphocytosis promoting factor or LPF) and 23.4 µg

>of FHA. The inactivated acellular pertussis component contributes not more

>than 50 endotoxin units (EU) to the endotoxin content of 1 mL of DTaP. The

>potency of the pertussis components is evaluated by measuring the antibody

>response to PT and FHA in immunized mice using an ELISA system.

>

>Acellular Pertussis Vaccine Concentrates (For Further Manufacturing Use)

>are produced by The Research Foundation for Microbial Diseases of Osaka

>University (BIKEN), Osaka, Japan under United States (US) license, and are

>combined with diphtheria and tetanus toxoids manufactured by CLI. The

>Tripedia® vaccine is filled, labeled, packaged, and released by CLI.

>

>TriHIBit®, when Tripedia® vaccine is used to reconstitute ActHIB® for the

>fourth dose only , each single dose of combined vaccine (0.5 mL) is

>formulated to contain 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid

>(both toxoids induce at least 2 units of antitoxin per mL in the guinea pig

>potency test), 46.8 µg of pertussis antigens (approximately 23.4 µg of

>inactivated PT and 23.4 µg of FHA), 10 µg of purified Haemophilus

>influenzae type b capsular polysaccharide conjugated to 24 µg of

>inactivated tetanus toxoid, and 8.5% sucrose.

>

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>

>

>

>CLINICAL PHARMACOLOGY

>

>

>Simultaneous immunization against diphtheria, tetanus, and pertussis, using

>a conventional " whole-cell " pertussis DTP vaccine (Diphtheria and Tetanus

>Toxoids and Pertussis Vaccine Adsorbed - For Pediatric Use), has been a

>routine practice during infancy and childhood in the US since the late

>1940s. This practice has played a major role in markedly reducing the

>incidence rates of cases and deaths from each of these diseases. 3

>

>Tripedia® vaccine combines CLI's diphtheria and tetanus toxoids with

>purified pertussis antigens (inactivated PT and FHA). These pertussis

>antigens have been used routinely for childhood vaccination in Japan since

>1981 4,5,6,7 and have been used for investigational purposes in Sweden,

>1,8,9,10,11 as well as in the US and Germany. 1,12,13,14,15 In the US,

>since 1992, Tripedia® vaccine has been indicated for immunization of

>children 15 months to 7 years of age (prior to the seventh birthday) who

>have previously been immunized with three or four doses of whole-cell

>pertussis DTP.

>

>

>

>

>

>DIPHTHERIA

>

>Corynebacterium diphtheriae may cause both localized and generalized

>disease. The systemic intoxication is caused by diphtheria exotoxin, an

>extracellular protein metabolite of toxigenic strains of C. diphtheriae .

>Protection against disease is due to the development of neutralizing

>antibody to diphtheria toxin.

>

>Both toxigenic and nontoxigenic strains of C. diphtheriae can cause

>disease, but only strains that produce diphtheria toxin cause severe

>manifestations, such as myocarditis and neuritis. Diphtheria remains a

>serious disease, with the highest case-fatality rates among infants and the

>elderly. 3

>

>At one time, diphtheria was common in the US. More than 200,000 cases,

>primarily among children, were reported in 1921. Approximately 5% to 10% of

>cases were fatal; the highest case-fatality rates were in the very young

>and the elderly. Reported cases of diphtheria of all types declined from

>306 in 1975 to 59 in 1979; most were cutaneous diphtheria reported from a

>single state. After 1979, cutaneous diphtheria was no longer reportable. 3

>>From 1980 to 1989, only 24 cases of respiratory diphtheria were reported in

>the US; 2 cases were fatal and 18 (75%) occurred among persons >/=20 years

>of age. 3 From 1990 through 1994, 15 cases were reported. 16

>

>Diphtheria is currently a rare disease in the US primarily because of the

>high level of appropriate vaccination among children (97% of children

>entering school have reached >/= three doses of diphtheria and tetanus

>toxoids and pertussis vaccine adsorbed [DTP]) and because of an apparent

>reduction in the circulation of toxigenic strains of C. diphtheriae . 3

>Most cases occur among unvaccinated or inadequately vaccinated persons. 3

>Diphtheria remains a serious disease in some areas of the world as

>evidenced by the recent outbreak in the former Soviet Union. 17

>

>Complete immunization significantly reduces the risk of developing

>diphtheria, and immunized persons who develop disease have milder illness.

>Protection is thought to last at least 10 years. Immunization does not,

>however, eliminate carriage of C. diphtheriae in the pharynx, nose or on

>the skin. 3

>

>Efficacy of CLI's diphtheria toxoid used in Tripedia® vaccine was

>determined on the basis of immunogenicity studies, with a comparison to a

>serological correlate of protection (0.01 antitoxin units/mL) established

>by the Panel on Review of Bacterial Vaccines & Toxoids. 18

>

>

>

>

>

>TETANUS

>

>Tetanus is an intoxication manifested primarily by neuromuscular

>dysfunction caused by a potent exotoxin elaborated by Clostridium tetani .

>

>The occurrence of tetanus in the US has decreased dramatically from 560

>reported cases in 1947 to an average of 57 cases reported annually from

>1985-1994. 16 Tetanus in the US is primarily a disease of older adults. Of

>99 tetanus patients with complete information reported to the Centers for

>Disease Control and Prevention (CDC) during 1987 and 1988, 68% were >/= 50

>years of age, while only six were < 20 years of age. Overall, the

>case-fatality rate was 21%. The disease continues to occur almost

>exclusively among persons who are unvaccinated or inadequately vaccinated

>or whose vaccination histories are unknown or uncertain. 3

>

>In 4% of tetanus cases reported during 1987 and 1988, no wound or other

>condition was implicated. Non-acute skin lesions, such as ulcers, or

>medical conditions, such as abscesses, were reported in 14% of cases. 3

>

>Spores of C. tetani are ubiquitous. Serological tests indicate that

>naturally acquired immunity to tetanus toxin does not occur in the US.

>Thus, universal primary immunization, with subsequent maintenance of

>adequate antitoxin levels by means of appropriately timed boosters, is

>necessary to protect all age groups. Tetanus toxoid is a highly effective

>antigen, and a completed primary series generally induces protective levels

>of serum antitoxin that persist for 10 or more years. 3

>

>Efficacy of CLI's tetanus toxoid used in Tripedia® vaccine was determined

>on the basis of immunogenicity studies, with a comparison to a serological

>correlate of protection (0.01 antitoxin units/mL) established by the Panel

>on Review of Bacterial Vaccines & Toxoids. 18

>

>

>

>

>

>PERTUSSIS

>

>Since pertussis became a nationally reportable disease in 1922, the highest

>number of pertussis cases (approximately 266,000) was reported in 1934.

>Following the licensure of whole-cell pertussis DTP vaccine in 1949 and the

>widespread use of DTP among infants and children, the incidence of reported

>pertussis declined to a historical low of 1,010 cases in 1976. However,

>since the early 1980s, reported pertussis incidence has increased with

>cyclical peaks occurring in 1983, 1986, 1990, and 1993. Following the peak

>in reported cases in 1993, the number declined during 1994 and the first 2

>quarters of 1995, a pattern consistent with the previously observed 3-4

>year periodicity in pertussis incidence. National pertussis surveillance

>data for January 1992-December 1994 during which an average of 5,095 cases

>were reported annually, demonstrate the continued effectiveness of the

>current pertussis vaccination program. 19

>

>Pertussis (whooping cough) is a disease of the respiratory tract caused by

>Bordetella pertussis . This gram-negative coccobacillus produces a variety

>of biologically active components. The role of the different components

>produced by B pertussis in either the pathogenesis of, or the immunity to,

>pertussis is not well understood. However, efficacy has been demonstrated

>for this vaccine that contained both inactivated PT and FHA.

>

>Pertussis is highly communicable (attack rates of > 90% have been reported

>among unvaccinated household contacts 20 ) and can cause severe disease,

>particularly among very young children. Of 10,749 patients < 1 year of age

>reported nationally as having pertussis during the period 1980 to 1989, 69%

>were hospitalized, 22% had pneumonia, 3.0% had one or more seizures, 0.9%

>had encephalopathy, and 0.6% died. 21

>

>In older children and adults, including some who were previously immunized,

>infection may result in nonspecific symptoms of bronchitis or an upper

>respiratory tract infection, and pertussis may not be diagnosed because

>classic signs, especially the inspiratory whoop, may be absent. Older

>preschool-aged children and school-aged siblings who are not fully

>immunized and develop pertussis may be important sources of infection for

>young infants, the group at highest risk of clinical disease and severe

>pertussis. 3 The infected adult may play a role in the transmission of

>pertussis. 22,23

>

>General use of whole-cell pertussis DTP vaccines has resulted in a

>substantial reduction in cases and deaths from pertussis disease. 20,24 The

>use of Tripedia® vaccine as a primary series evokes an antibody response

>with respect to PT and FHA and has been shown to be effective in clinical

>studies. 1

>

>Acellular pertussis vaccines have been used in Japan since 1981, mostly in

>2-year-old children. Evidence for the efficacy of these vaccines, as a

>group, is demonstrated by the decline in pertussis disease with their

>routine use in that country. 4,20 In addition, a review of epidemiological

>studies of the Japanese acellular pertussis vaccines estimated that these

>vaccines, as a group, were 88% efficacious in protecting against clinical

>pertussis on household exposure, with a 95% confidence interval (CI) of 79%

>to 93%. 25

>

>Two clinical studies were conducted to assess the protective efficacy of

>these acellular pertussis components of Tripedia® vaccine. A randomized,

>controlled clinical trial in Sweden assessed efficacy after only two doses

>of the pertussis component in children 5 to 11 months of age. 10 A second

>study was conducted in Germany using a three-dose schedule to evaluate the

>protective efficacy of the Tripedia® vaccine in younger infants.

>

>In 1986-1987, a double-blind, randomized, placebo-controlled efficacy trial

>of two BIKEN acellular pertussis vaccines was conducted in Sweden. One of

>the vaccines was a two-component vaccine comparable to the acellular

>pertussis components contained in Tripedia® vaccine. This prospective trial

>used a standardized case definition and active case ascertainment. In this

>trial, 1,389 children, 5 to 11 months of age (median 8.5 months), received

>two doses of the acellular pertussis vaccine 7 to 13 weeks apart and 954

>received a placebo control. During the 15 months of follow-up from 30 days

>after the second dose, culture-confirmed whooping cough (cough of any

>duration and a positive culture of B pertussis ) occurred in 40 placebo and

>18 acellular pertussis vaccine recipients. The point estimate of protective

>efficacy for two doses of vaccine was 69% (95% CI; 47% to 82%) for all

>cases of culture-confirmed pertussis with any cough 1 day or longer and 79%

>(95% CI; 57% to 90%) using a secondary case definition of culture-confirmed

>cases with cough of over 30 days duration. 10 In a reanalysis of the

>Swedish data efficacy estimates increased with duration of coughing spasms

>and when the case definition included whoops and whoops plus at least nine

>coughing spasms a day. 26 Using a case definition of cough of 21 days or

>more of coughing spasms, confirmed by positive culture resulted in an

>efficacy estimate of 81% (95% CI; 61% to 90%). 26

>

>Using a passive reporting system, three-year unblinded follow-up of vaccine

>and placebo recipients from the above Swedish study has shown a post-trial

>efficacy of 77% (95% CI; 65% to 85%) for all culture-proven cases of

>pertussis, and an efficacy of 92% (95% CI; 84% to 96%) for culture-proven

>cases with a cough of over 30 days duration. 27

>

>A case-control study to evaluate the efficacy of Tripedia® vaccine was

>conducted in Germany. The study population consisted of patients in 63

>pediatric practices who had no contraindications to pertussis immunization

>and were enrolled in the study between the ages of 6 and 17 weeks (actual

>range of age at first visit was up to 20 weeks for the DT group). By

>parental choice, infants received Tripedia® vaccine or whole-cell pertussis

>DTP (Behringwerke, Germany) at approximately 3, 5, and 7 months of age, or

>DT, or no vaccine. Cases of pertussis were identified by obtaining cultures

>for B pertussis from all patients between the ages of 2 and 24 months who

>presented to the physician's office with 7 or more days of cough.

>Identification of presumptive cases of pertussis was made by primary care

>physicians who were not blinded to the vaccine status of subjects. Cases

>were confirmed by positive culture in the subject or positive culture in a

>subject's household contact. Duration of cough in study subjects was

>determined at an office visit, by telephone, or by home visit 21-24 days

>after the onset of cough.

>

>Four aged-matched controls were selected for each case from the same

>pediatric practice. Selection of controls was done without knowledge of

>vaccination status. The vaccine (or no vaccine) and number of doses which

>each case and control subjects received subsequently was determined from

>medical records.

>

>In order to adjust for potentially confounding variables, information on

>sex, race, day-care attendance, well-baby visits, sick-child visits,

>pertussis vaccination status of siblings, age of siblings, number of

>siblings, day-care attendance of siblings, and parental employment status

>was obtained through interview of parents. Information on erythromycin use

>was not obtained for the study population.

>

>A total of 16,780 infants were enrolled in the study, of whom 74.6%

>received Tripedia® vaccine and 10.9%, 12.5%, and 2.1% received DTP, DT, or

>no vaccine, respectively, by non-random parental choice. A total of 11,017

>cultures for B pertussis was obtained and 140 cases were identified using a

>primary case definition of cough >/= 21 days, plus positive culture for B

>pertussis or household contact with a person with culture-positive

>pertussis. Of the 140 cases, 130 cases were diagnosed on the basis of a

>positive culture and 10 on the basis of household contact with a

>culture-positive case. For the 140 cases, 543 controls were selected. Of

>the 140 cases, 29 (20.7%) received three doses of DTaP, 5 (3.6%) received

>two doses of DTaP, 44 (31.4%) received two or three doses of DT vaccine, 44

>(31.4%) received one dose of either DTaP, whole-cell pertussis DTP or DT,

>and 18 (13%) received no vaccine. Of the 543 controls, 175 (32.2%) received

>three doses of DTaP, 67 (12.3%) received two doses of DTaP, 45 (8.3%)

>received two or three doses of whole-cell pertussis DTP, 73 (13.4%)

>received DT vaccine, 153 (28.2%) received one dose of either DT, DTP, or

>DTaP, and 30 (5.5%) received no vaccine. Adjusting for sibling age, sibling

>pertussis immunization by age group, siblings in day care, number of

>siblings in day care, and father's employment status, the vaccine efficacy

>of three doses of Tripedia® vaccine compared to two or three doses of DT

>was 80% (95% CI; 59% to 90%). 1

>

>In a clinical study conducted in 65 US and 89 German infants, a single lot

>of Tripedia® vaccine was administered at 2, 4 and 6 months of age for the

>purpose of comparing immune responses to PT and FHA. This study showed that

>US and German infants, who received three doses of Tripedia® vaccine,

>expressed similar antibody responses to these antigens. The percentage of

>infants demonstrating a four-fold or greater antibody response, was also

>similar for PT and FHA in both groups. 1

>

>In a clinical study, US infants received Tripedia®, ActHIB®, OPV, and

>hepatitis B vaccines simultaneously. In one of the study groups, Tripedia®,

>ActHIB® and OPV were administered at 2, 4, and 6 months of age and

>hepatitis B was given at 2 and 4 months of age. One hundred percent of the

>69 children who received ActHIB® simultaneously with Tripedia® vaccine

>demonstrated anti-PRP antibodies >/= 1 µg/mL. Sera from a subset of 12

>infants who received hepatitis B simultaneously at 2 and 4 months of age

>showed that 93% had antiHBs titers of > 10 mIU/mL. Sera from a subset of 20

>infants who received OPV simultaneously at 2, 4, and 6 months of age showed

>that 100% had protective neutralizing antibody responses to all three polio

>virus types.

>

>

>

>TRIPEDIA® COMBINED WITH ActHIB®, TriHIBit®, BY RECONSTITUTION

>

>

>Clinical studies examined the immune response in 15- to 20-month-old

>children when Tripedia® vaccine was used to reconstitute one lyophilized

>single dose vial of ActHIB® (TriHIBit®). All children received three doses

>of Haemophilus b Conjugate Vaccine (ActHIB® or HibTITER®) and three doses

>of whole-cell DTP at approximately 2, 4, and 6 months of age. Table 1 shows

>the diphtheria, tetanus and pertussis responses when Tripedia® vaccine was

>used to reconstitute ActHIB® (TriHIBit®) compared to the two vaccines given

>concomitantly but at different sites. In children who received the vaccines

>separately or combined, 100% had an antibody response to the PRP component

>>/= 1.0 µg/mL. 1

>

>

>

>

>

>

>

>

>

>TABLE 1 1 IMMUNE RESPONSES IN 15- TO 20-MONTH-OLD CHILDREN WHEN

>TRIPEDIA® VACCINE IS COMBINED WITH ActHIB® BY RECONSTITUTION (TriHIBit®)

>COMPARED TO THE VACCINES ADMINISTERED SEPARATELY

>

> PRE-DOSE POST-DOSE

> VACCINE GROUP N </nurse/static.htm?path=pdrel/pdr/62470460.htm#F01>*

>TriHIBit®

>92-93 Separate

>102-103 TriHIBit®

>93 Separate

>98

> Anti-LPF

> GMT (ELISA units/mL)

> % 4-Fold Rise 26.30

>- 24.56

>- 471.00

>87.0 363.90

>85.7

> Anti-LPF

> GMT (CHO CELL)

> % 4-Fold Rise 33.48

>- 31.78

>- 806.70

>92.3 701.60

>90.6

> Anti-FHA

> GMT (ELISA units/mL)

> % 4-Fold Rise 3.83

>- 3.61

>- 44.68

>68.5 </nurse/static.htm?path=pdrel/pdr/62470460.htm#F02>** 38.81

>80.6

> Diphtheria Antitoxin

> GMT (units/mL)

> > 0.01 u/mL 0.15

>- 0.16

>- 6.31

>100.00 6.65

>100.00

> Tetanus Antitoxin

> GMT (equivalents/mL)

> > 0.01 u/mL 0.05

>- 0.06

>- 1.10

>100.00 1.15

>100.00

> * N = number of children

> ** The clinical significance of the difference in 4-fold rise of anti-FHA

>is unknown at present.

>

>

>

>In clinical studies evaluating simultaneous administration of Tripedia® and

>ActHIB® with MMR vaccine to 15- to 20-month-old children, the data suggest

>that the combination vaccine does not interfere with the immunogenicity of

>the MMR vaccine. Overall seroconversion rates in children who received

>ActHIB® reconstituted with Tripedia® (TriHIBit®) vaccine were 98% (46/47),

>98% (42/43) and 96% (43/45) for measles, mumps and rubella, respectively.

>

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>

>

>

>INDICATIONS AND USAGE

>

>

>Tripedia® vaccine is indicated for active immunization against diphtheria,

>tetanus and pertussis (whooping cough) simultaneously in infants and

>children 6 weeks to 7 years of age (prior to seventh birthday). Because of

>the substantial risks of complications of the disease, completion of a

>primary series of pertussis vaccine early in life is strongly recommended.

>3 However, in instances where the pertussis vaccine component is

>contraindicated, Diphtheria and Tetanus Toxoids Adsorbed (For Pediatric

>Use) (DT) should be used for each of the remaining doses. (See

></nurse/static.htm?path=pdrel/pdr/62470460.htm#T05>CONTRAINDICATIONS

>section.)

>

>When Tripedia® vaccine is used to reconstitute ActHIB® (TriHIBit®), the

>combined vaccines are indicated for the active immunization of children 15

>to 18 months of age who have previously been immunized against diphtheria,

>tetanus and pertussis with three doses consisting of either whole-cell

>pertussis DTP or acellular pertussis vaccine and three or fewer doses of

>ActHIB® (OmniHIB®) within the first year of life for the prevention of

>invasive diseases caused by H influenzae type b and caused by diphtheria,

>tetanus, and pertussis. 1 (Refer to ActHIB® package insert.)

>

>If passive immunization is required, Tetanus Immune Globulin (Human) (TIG)

>and/or equine Diphtheria Antitoxin should be used.

>

>Persons who have recovered from culture-confirmed pertussis do not need

>additional doses of Tripedia® vaccine but should receive additional doses

>of DT to complete the series.

>

>Tripedia® vaccine is not to be used for treatment of B. pertussis, C.

>diphtheriae, or C. tetani infections.

>

>As with any vaccine, vaccination with Tripedia® vaccine may not protect

>100% of susceptible individuals.

>

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>

>

>

>CONTRAINDICATIONS

>

>

>Hypersensitivity to any component of the vaccine, including thimerosal and

>gelatin, is a contraindication.

>

>It is a contraindication to use this vaccine after an immediate

>anaphylactic reaction temporally associated with a previous dose. Because

>of uncertainty as to which component of the vaccine might be responsible,

>no further vaccination with diphtheria, tetanus, or pertussis components

>should be carried out. Alternatively, because of the importance of tetanus

>vaccination, such individuals may be referred for evaluation by an

>allergist. 3

>

>Immunization should be deferred during the course of an acute febrile

>illness. The decision to administer or delay vaccination because of a

>current or recent febrile illness depends on the severity of symptoms and

>on the etiology of the disease. All vaccines can be administered to persons

>with mild illness such as diarrhea, mild upper-respiratory infection with

>or without low-grade fever, or other low grade febrile illness. 28

>

>Elective immunization procedures should be deferred during an outbreak of

>poliomyelitis. 29

>

>Encephalopathy not due to an identifiable cause, occurring within 7 days of

>a prior whole-cell pertussis DTP or DTaP immunization and consisting of

>major alterations of consciousness, unresponsiveness, generalized or focal

>seizures that persist for more than a few hours and failure to recover

>within 24 hours should be considered a contraindication to further use;

>this includes severe alterations in consciousness with generalized or focal

>neurologic signs. Even though causation cannot be established, no

>subsequent doses of pertussis vaccine should be given. 3

>

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>

>

>

>WARNINGS

>

>

>This product contains dry natural latex rubber as follows: The stopper to

>the vial contains dry natural latex rubber.

>

>If any of the following events occurs in temporal relation with the receipt

>of either whole-cell pertussis DTP or DTaP, the decision to administer

>subsequent doses of vaccine containing the pertussis component should be

>carefully considered. Although these events were once considered

>contraindications to whole-cell pertussis DTP, there may be circumstances,

>such as high incidence of pertussis, in which the potential benefits

>outweigh the possible risks, particularly since the following events have

>not been proven to cause permanent sequelae: 3,30

>

>

> * Temperature of >/= 40.5°C (105°F) within 48 hours, not due to another

>identifiable cause.

>* Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48

>hours.

>* Persistent, inconsolable crying lasting >/= 3 hours, occurring within 48

>hours.

>* Convulsions with or without fever, occurring within 3 days.

>

>A recent clinical study suggests that persistent, inconsolable crying

>lasting at least 3 hours following vaccination with Tripedia® vaccine may

>occur less frequently than has been observed historically for DTP vaccine.

>1,31

>

>When a decision is made to withhold the pertussis component, immunization

>with DT should be continued.

>

>Tripedia® vaccine should not be given to children with any coagulation

>disorder, including thrombocytopenia, that would contraindicate

>intramuscular injection unless the potential benefit clearly outweighs the

>risk of administration.

>

>In the opinion of the manufacturer, seizure disorder in children before or

>after any immunization with Tripedia® is considered a warning against

>further immunization with this vaccine. Recent studies suggest that infants

>and children with a history of convulsions in first-degree family members

>(i.e., siblings and parents) have a 3.2-fold increased risk for neurologic

>events compared with those without such histories when given DTP. 25,32

>However, the ACIP has concluded that a family history of convulsions in

>parents and siblings is not a contraindication to pertussis vaccination and

>that children with such family histories should receive pertussis vaccine

>according to the recommended schedule. 3,20,28

>

>In children with a history of febrile or non-febrile convulsions,

>acetaminophen should be given at the time of Tripedia® vaccination

>according to acetaminophen package insert recommended dosage to reduce the

>possibility of post-vaccination fever. 3,20,28

>

>A committee of the Institute of Medicine (IOM) has concluded that evidence

>is consistent with a causal relationship between DTP and acute neurologic

>illness, and under special circumstances, between DTP and chronic

>neurologic disease in the context of the NCES report. 33,34 However, the

>IOM committee concluded that the evidence was insufficient to indicate

>whether or not DTP increased the overall risk of chronic neurologic

>disease. 34 Acute encephalopathy or permanent neurological injury, have not

>been reported in temporal association after administration of Tripedia®

>vaccine but the experience with this vaccine is insufficient to rule this

>out. (See </nurse/static.htm?path=pdrel/pdr/62470460.htm#V05>ADVERSE

>REACTIONS section.)

>

>Infants and children with recognized possible or potential underlying

>neurologic conditions seem to be at enhanced risk for the appearance of

>manifestations of the underlying neurologic disorder within two or three

>days following whole-cell pertussis vaccination. 3 Whether to administer

>Tripedia® vaccine to children with proven or suspected underlying

>neurologic disorders must be decided on an individual basis. Important

>considerations include the current local incidence of pertussis. 3

>

>Tripedia® vaccine should not be combined through reconstitution with any

>vaccine for administration to infants younger than 15 months of age.

>Tripedia® vaccine should not be reconstituted with any vaccine other than

>ActHIB® (OmniHIB®) for children 15 months of age or older.

>

>(<JavaScript:GotoTop();>back to top)

>

>

>

>PRECAUTIONS

>

>

>

>

>GENERAL

>

>Care is to be taken by the health-care provider for the safe and effective

>use of this vaccine.

>

>EPINEPHRINE INJECTION (1:1000) MUST BE IMMEDIATELY AVAILABLE SHOULD AN

>ACUTE ANAPHYLACTIC REACTION OCCUR DUE TO ANY COMPONENT OF THE VACCINE.

>

>Prior to an injection of any vaccine, all known precautions should be taken

>to prevent adverse reactions. This includes a review of the patient's

>history with respect to possible sensitivity and any previous adverse

>reactions to the vaccine or similar vaccines, and to possible sensitivity

>to dry natural latex rubber, previous immunization history, current health

>status (see

></nurse/static.htm?path=pdrel/pdr/62470460.htm#T05>CONTRAINDICATIONS

>section), and a current knowledge of the literature concerning the use of

>the vaccine under consideration. Immunosuppressed patients may not respond.

>Tripedia® vaccine is not contraindicated in patients with HIV infection. 3

>

>Special care should be taken to ensure that the injection does not enter a

>blood vessel.

>

>A separate, sterile syringe and needle or a sterile disposable unit should

>be used for each patient to prevent transmission of hepatitis or other

>infectious agents from person to person. Needles should not be recapped but

>should be disposed of properly.

>

>

>

>

>

>INFORMATION FOR PATIENT

>

>Parents should be fully informed of the benefits and risks of immunization

>with Tripedia® vaccine.

>

>The physician should inform the parents or guardians about the potential

>for adverse reactions that have been temporally associated with Tripedia®

>and other pertussis vaccine administration. The health-care provider should

>provide the Vaccine Information Materials (VIMs) which are required by the

>National Childhood Vaccine Injury Act of 1986 to be given with each

>immunization. Parents or guardians should be instructed to report any

>serious adverse reactions to their health-care provider.

>

>IT IS EXTREMELY IMPORTANT WHEN A CHILD IS RETURNED FOR THE NEXT DOSE IN THE

>SERIES THAT THE PARENT SHOULD BE QUESTIONED CONCERNING OCCURRENCE OF ANY

>SYMPTOMS AND/OR SIGNS OF AN ADVERSE REACTION AFTER THE PREVIOUS DOSE OF THE

>SAME VACCINE (SEE

></nurse/static.htm?path=pdrel/pdr/62470460.htm#T05>CONTRAINDICATIONS AND

></nurse/static.htm?path=pdrel/pdr/62470460.htm#V05>ADVERSE REACTIONS

>SECTIONS).

>

>The health-care provider should inform the parent or guardian of the

>importance of completing the pertussis immunization series, unless a

>contraindication to further immunization exists.

>

>The US Department of Health and Human Services has established a Vaccine

>Adverse Event Reporting System (VAERS) to accept all reports of suspected

>adverse events after the administration of any vaccine, including but not

>limited to the reporting of events required by the National Childhood

>Vaccine Injury Act of 1986. 35 The toll-free number for VAERS forms and

>information is 1-800-822-7967.

>

>The National Vaccine Injury Compensation Program, established by the

>National Childhood Vaccine Injury Act of 1986, requires physicians and

>other health-care providers who administer vaccines to maintain permanent

>vaccination records and to report occurrences of certain adverse events to

>the US Department of Health and Human Services. Reportable events include

>those listed in the Act (i.e., those listed in the vaccine injury table)

>for each vaccine and events specified in the package insert as

>contraindications to further doses of the vaccine. 36,37

>

>(<JavaScript:GotoTop();>back to top)

>

>DRUG INTERACTIONS

>

>

>As with other IM injections use with caution in patients on anticoagulant

>therapy.

>

>Immunosuppressive therapies, including irradiation, antimetabolites,

>alkylating agents, cytotoxic drugs, and corticosteroids (used in greater

>than physiologic doses), may reduce the immune response to vaccines.

>Although no specific studies with pertussis vaccine are available, if

>immunosuppressive therapy will be discontinued shortly, it would be

>reasonable to defer immunization until the patient has been off therapy for

>one month; otherwise, the patient should be vaccinated while still on

>therapy. 3

>

>For information regarding simultaneous administration with other vaccines

>refer to </nurse/static.htm?path=pdrel/pdr/62470460.htm#G05>DOSAGE AND

>ADMINISTRATION section.

>

>If Tripedia® vaccine has been administered to persons receiving

>immunosuppressive therapy, a recent injection of immune globulin or having

>an immunodeficiency disorder, an adequate immunologic response may not be

>obtained.

>

>Tetanus Immune Globulin, or Diphtheria Antitoxin, if used, should be given

>in a separate site, with a separate needle and syringe.

>

>The combination of Tripedia® vaccine with other vaccines has not been

>evaluated for safety and immunogenicity in infants younger than 15 months

>of age. The combination of Tripedia® vaccine with any vaccine other than

>ActHIB® (OmniHIB®) has not been evaluated for safety and immunogenicity in

>infants 15 months of age or older.

>

>

>

>

>

>CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

>

>Tripedia® vaccine has not been evaluated for its carcinogenic or mutagenic

>potentials or impairment of fertility.

>

>

>

>PREGNANCY

>

>

>REPRODUCTIVE STUDIES--PREGNANCY CATEGORY C

>

>Animal reproduction studies have not been conducted with Tripedia® vaccine.

>It is not known whether Tripedia® vaccine can cause fetal harm when

>administered to a pregnant woman or can affect reproductive capacity.

>Tripedia® vaccine is NOT recommended for use in a pregnant woman.

>

>PEDIATRIC USE

>

>SAFETY AND EFFECTIVENESS OF TRIPEDIA® VACCINE IN INFANTS BELOW SIX WEEKS OF

>AGE HAVE NOT BEEN ESTABLISHED. (SEE

></nurse/static.htm?path=pdrel/pdr/62470460.htm#G05>DOSAGE AND

>ADMINISTRATION SECTION.)

>

>THIS VACCINE IS NOT RECOMMENDED FOR PERSONS 7 YEARS OF AGE AND OLDER.

>Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) is to be used in

>individuals 7 years of age or older.

>

>Tripedia® vaccine should not be combined through reconstitution with any

>vaccine for administration to infants younger than 15 months of age.

>Tripedia® vaccine can only be combined with ActHIB® (OmniHIB®) by

>reconstitution for children 15 months of age or older.

>

>(<JavaScript:GotoTop();>back to top)

>

>

>

>ADVERSE REACTIONS

>

>

>A total of 11,400 doses of Tripedia® vaccine has been administered in US

>clinical trials in children 2 to 6 months, 15 to 20 months of age or 4 to 6

>years of age. When compared to CLI's whole-cell pertussis DTP vaccine,

>Tripedia® vaccine produced fewer local reactions such as erythema,

>swelling, and tenderness at the injection site and fewer systemic reactions

>such as fever, irritability, drowsiness, vomiting, anorexia and

>high-pitched unusual cry. 1 In a double-blind, comparative US trial, 673

>infants were randomized to receive either 3 doses of Tripedia® vaccine or

>CLI's DTP vaccine (Table 2). 1 Safety data are available for 672 infants.

>Rates for all reported local reactions and other reactions such as fever >

>101°F, irritability, drowsiness, and anorexia were significantly less in

>Tripedia® vaccine recipients. In contrast to whole-cell pertussis DTP, no

>hypotonic-hyporesponsive episodes occurred in Tripedia® vaccine recipients.

>Reaction rates generally peaked within the first 24 hours, and decreased

>substantially over the next two days. 1,14,15

>

>

>

>

>

>

>

>

>

>TABLE 2 1 ADVERSE EVENTS OCCURRING WITHIN 72 HOURS FOLLOWING DIPHTHERIA

>AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE ADSORBED TRIPEDIA®)

>IMMUNIZATIONS GIVEN TO INFANTS 2 TO 6 MONTHS OF AGE

>

> FREQUENCY

> EVENT TRIPEDIA®

>REACTION % WHOLE-CELL PERTUSSIS DTP

>REACTION %

> Dose 1 Dose 2 Dose 3 Dose 1 Dose 2 Dose 3

> No. of Infants </nurse/static.htm?path=pdrel/pdr/62470460.htm#F05>**/*

>505 499 490 167 159 152

> Local

> Erythema </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 9.0 9.8

>16.9 28.3 32.9 32.9

> Erythema > 1 " </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 1.2

> 1.8 2.2 7.8 8.4 7.4

> Swelling </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 6.4 4.5

>6.5 28.3 23.9 27.5

> Swelling > 1 " </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 1.4

> 0.6 1.0 12.7 11.0 11.4

> Tenderness </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 11.8

>6.7 7.1 50.6 44.2 42.6

> Systemic

> Fever > 101°F (rectal)

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 0.4 1.6 3.5 3.6

>7.5 11.2

> Irritability </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 35.3

>30.1 27.1 72.9 71.8 57.7

> Drowsiness </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 39.4

>17.6 15.9 59.6 45.2 25.5

> Anorexia </nurse/static.htm?path=pdrel/pdr/62470460.htm#F03>* 6.0 5.3

>5.7 26.5 20.0 18.8

> Vomiting 6.0 </nurse/static.htm?path=pdrel/pdr/62470460.htm#F04>** 5.5

> 3.7 10.8 7.1 2.7

> High-pitched cry 2.4 1.0 1.4 10.8 5.8 3.4

> Persistent cry 0.2 0.2 0.8 3.0 1.3 2.0

> * p < 0.01 when compared to whole-cell pertussis DTP for all doses.

> ** p < 0.05 when compared to whole-cell pertussis DTP.

> **/* For certain adverse events information was not available for a small

>number of infants.

>

>

>

>Adverse event data for Tables 2-6 were actively collected using patient

>diaries, phone call follow-up and/or by questioning the parent(s) at clinic

>visits. All data were recorded on standardized case report forms.

>

>A similar reduction in adverse events was seen in a randomized,

>double-blind, comparative trial conducted in the US by the National

>Institutes of Health (NIH) when Tripedia® vaccine was compared to Lederle

>Laboratories whole-cell pertussis DTP vaccine (Table 3). 38 Each data point

>presented in Table 3 is a summary of the frequency of reactions following

>any of the three primary immunizing doses. Local adverse reactions which

>include pain, erythema, swelling, and systemic reactions such as fever,

>anorexia, vomiting, drowsiness and fussiness may occur following any of the

>three primary vaccinations.

>

>

>

>

>

>

>

>

>

>TABLE 3 38 PERCENT OF INFANTS WHO WERE REPORTED TO HAVE HAD THE

>INDICATED REACTION BY THE THIRD EVENING AFTER ANY OF THE FIRST THREE DOSES

>OF WHOLE-CELL PERTUSSIS DTP OR DTaP

>

> N </nurse/static.htm?path=pdrel/pdr/62470460.htm#F10>¶ ERYTHEMA

>SWELLING PAIN </nurse/static.htm?path=pdrel/pdr/62470460.htm#F08>**/*

>FEVER </nurse/static.htm?path=pdrel/pdr/62470460.htm#F06>*

>>101°F ANOREXIA VOMITING DROWSINESS FUSSINESS

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F09>**/**

> Tripedia® 135 32.6

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 20.0

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 9.6

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 5.2

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 22.2

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 7.4 41.5

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>** 19.3

></nurse/static.htm?path=pdrel/pdr/62470460.htm#F07>**

> Whole-Cell

> Pertussis DTP 371 72.7 60.9 40.2 15.9 35.0 13.7 62.0 41.5

> * Rectal Temperatures

> **p < 0.01 when compared to whole-cell pertussis DTP.

> **/* Moderate or severe = cried or protested to touch or when leg moved.

> **/** Moderate or severe = prolonged or persistent crying that could not

>be comforted and refusal to play.

> ¶ N = Number of infants

>

>

>

>The frequency of adverse reactions following each dose in children who

>received only Tripedia® vaccine is shown in Table 4. 1,38 Of the 135

>infants who received Tripedia® vaccine at 2, 4, and 6 months of age, a

>subset of 82 received a fourth dose of Tripedia® vaccine and a subset of 18

>received a fifth dose of Tripedia® vaccine.

>

>

>

>

>

>

>

>

>

>TABLE 4 1,38 ADVERSE EVENTS (%) OCCURRING WITHIN 72 HOURS FOLLOWING EACH

>DOSE OF DIPHTHERIA AND TETANUS TOXOID AND ACELLULAR PERTUSSIS VACCINE

>(TRIPEDIA®) VACCINATION IN CHILDREN IN WHICH ALL DOSES WERE TRIPEDIA® VACCINE

>

>

>

>

>EVENT

> PRIMARY

>(N = 135 INFANTS) BOOSTER

>(N = 82 CHILDREN)

>(N = 18 CHILDREN)

> DOSE 1

>2 Months DOSE 2

>4 Months DOSE 3

>6 Months DOSE 4

>15 to 20 Months DOSE 5

>4 to 6 Years

> Local

> Erythema 12.6 12.7 19.1 17.1 33.3

> Swelling 8.8 8.2 10.7 15.9 27.8

> Pain </nurse/static.htm?path=pdrel/pdr/62470460.htm#F11>* 8.1 3.7 2.3

> 7.3 11.1

> Systemic

> Fever > 101°F </nurse/static.htm?path=pdrel/pdr/62470460.htm#F13>**/*

>0.7 1.4 3.1 2.4 0

> Anorexia 8.1 9.7 9.9 8.5 0

> Vomiting 5.2 1.5 2.3 2.4 0

> Drowsiness 28.9 17.9 4.6 6.1 5.6

> Fussiness </nurse/static.htm?path=pdrel/pdr/62470460.htm#F12>** 8.1

>7.4 7.6 3.7 0

> * Moderate or severe = cried or protested to touch or when leg moved.

> ** Moderate or severe = prolonged or persistent crying that could not be

>comforted and refusal to play.

> **/* Rectal temperatures for primary series, oral temperatures for Dose 4

>and Dose 5.

>

>

>

>In an open label US study additional data are available in 15- to

>20-month-old children who had previously received three doses of either

>Tripedia® vaccine (n = 109) or whole-cell pertussis DTP (n = 30). 39

>Reaction rates are presented in Table 5. Data on 738 children (a subset of

>the German case control study) receiving a fourth dose of Tripedia® vaccine

>in an open label study showed local and systemic reaction rates in the day

>following vaccination as follows: erythema (36.7%), erythema > 1 inch

>(12.5%), swelling (20.2%), pain (14%), temperature >/= 100.4°F (10.6%),

>irritability (14.6%), anorexia (8.4%), and persistent crying > 3 hours

>(0.4%). 1

>

>

>

>

>

>

>

>

>

>TABLE 5 1,39 COMPARISON OF ADVERSE EVENTS (%) OCCURRING WITHIN 72 HOURS

>FOLLOWING VACCINATION WITH

>TRIPEDIA® VACCINE IN CHILDREN WHO HAD RECEIVED THREE PREVIOUS DOSES OF

>TRIPEDIA® VACCINE OR THREE DOSES

>OF WHOLE-CELL PERTUSSIS DTP

>

> N ERY-

>THEMA

>>/=1 INCH SWELL-

>ING

>>/=1 INCH PAIN TEMPER-

>ATURE

>>/=

>101°F IRRIT-

>ABIL-

>ITY

> Tripedia® Primed 109 30.3 29.4 19.3 5.5 19.3

> Whole-Cell pertussis

> DTP Primed 30 23.3 20.0 10.3 3.3 13.3

>

>

>

>Table 6 lists the frequency of adverse reactions in 372 US children who

>received Tripedia® vaccine at 15 to 20 months of age and 240 US children

>who received Tripedia® vaccine at 4 to 6 years of age in a study conducted

>from 1989-1990. These children had previously received three or four doses

>of whole-cell pertussis DTP vaccine at approximately 2, 4, 6, and 18 months

>of age. 1

>

>

>

>

>

>

>

>

>

>TABLE 6 1 ADVERSE EVENTS (%) OCCURRING WITHIN 72 HOURS FOLLOWING DIPHTHERIA

>AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE ADSORBED (TRIPEDIA®)

>IMMUNIZATIONS GIVEN AT 15 TO 20 MONTHS AND 4 TO 6 YEARS OF AGE IN CHILDREN

>WHO HAD RECEIVED THREE OR FOUR DOSES OF DTP

>

>

>

>EVENT

> 15 TO 20 MONTHS

>THREE PREVIOUS

>DTP DOSES

>REACTION %

>(N = 372 CHILDREN) 4 TO 6 YEARS

>FOUR PREVIOUS

>DTP DOSES

>REACTION %

>(N = 240 CHILDREN)

> Local

> Erythema </nurse/static.htm?path=pdrel/pdr/62470460.htm#F14>* 18.3 31.3

> Swelling </nurse/static.htm?path=pdrel/pdr/62470460.htm#F15>** 10.8

>27.9

> Tenderness 14.2 46.2

> Systemic

> Fever > 101°F 4.7 4.8

> Diarrhea 6.3 0.8

> Vomiting 2.2 1.7

> Anorexia 7.8 5.4

> Drowsiness 12.4 15.0

> Irritability 21.2 15.8

> High-pitched

> unusual cry 1.1 </nurse/static.htm?path=pdrel/pdr/62470460.htm#F16>NA

> * Includes all occurrences of erythema.

> ** Includes all occurrences of swelling.

> NA Data not collected in this age group.

>

>

>

>The results of an open label, non-controlled clinical study, of 2,457 US

>children and targeted to evaluate less common and more severe adverse

>events following three doses of Tripedia® vaccine in the primary series are

>shown in Table 7. 1 Data were collected by parental interview at subsequent

>immunizations, chart review and telephone calls to the parents 60 days

>after the third dose.

>

>

>

>

>

>

>

>

>

>TABLE 7 1 MODERATELY SEVERE ADVERSE EVENTS OCCURRING WITHIN 48 HOURS

>FOLLOWING VACCINATION WITH TRIPEDIA® AT 2, 4, OR 6 MONTHS OF AGE (N = 7,102

>DOSES)

>

> EVENT NUMBER RATE/

>1,000

>DOSES

> Fever >/= 105°F 2 0.28

> Hypotonic/

> Hyporesponsive

> Episode 1 0.14

> Persistent cry

> >/= 3 hours 4 0.56

> Convulsions </nurse/static.htm?path=pdrel/pdr/62470460.htm#F17>* 0 0

> *One seizure episode was noted between 48 and 72 hours.

>

>

>

>Adverse experiences that are more serious and less common than those

>reported in Table 7 are not known at this time.

>

>In the large German efficacy study that enrolled 16,780 infants, 12,514 of

>whom received 41,615 doses of Tripedia® vaccine, hospitalization rates and

>death rates were similar between Tripedia® vaccine and DT recipients. 1

>Adverse events were monitored by spontaneous reporting by parents and a

>medical history obtained at each subsequent vaccination. Adverse events

>(rates per 1,000 doses) occurring within 7 days including those events

>interpreted by the investigator as related as well as those interpreted as

>unrelated to vaccination included; unusual cry (0.96), persistent cry > 3

>hours (0.12), febrile seizure (0.05), afebrile seizure (0.02) and

>hypotonic/hyporesponsive episodes (0.05). In contrast to the first Swedish

>pertussis efficacy trial conducted in 1986-87, 10 no deaths due to invasive

>bacterial infections were reported.

>

>Rarely, an anaphylactic reaction (i.e., hives, swelling of the mouth,

>difficulty breathing, hypotension, or shock) has been reported after

>receiving preparations containing diphtheria, tetanus, and/or pertussis

>antigens. 3

>

>Arthus-type hypersensitivity reactions, characterized by severe local

>reactions (generally starting 2 to 8 hours after an injection), may follow

>receipt of tetanus toxoid. A few cases of peripheral neuropathy have been

>reported following tetanus toxoid administration, although the evidence is

>inadequate to accept or reject a causal relation. 40

>

>Whole-cell pertussis DTP has been associated with acute encephalopathy. 33

>A 10-year follow-up to the National Childhood Encephalopathy Study (NCES)

>of children who experienced acute neurologic disorders in infancy concluded

>that serious acute neurologic illness increased the risk of chronic

>neurologic disease or death. 41 A committee of the Institute of Medicine

>(IOM) has concluded that, because DTP may cause acute neurologic illness,

>DTP may also cause chronic neurologic disease in the context of the NCES

>report. 34 However the IOM committee concluded that the evidence was

>insufficient to indicate whether or not DTP increased the overall risk of

>chronic neurologic disease. 34

>

>Sudden Infant Death Syndrome (SIDS) has occurred in infants following

>administration of whole-cell pertussis DTP and DTaP. Large case-control

>studies of SIDS in the US have shown that receipt of whole-cell pertussis

>DTP was not causally related to SIDS. 42,43,44 It should be recognized that

>the first three primary immunizing doses of whole-cell pertussis DTP and

>DTaP are usually administered to infants 2 to 6 months old and that

>approximately 85% of SIDS cases occur at ages 1 to 6 months, with the peak

>incidence occurring at 6 weeks to 4 months of age. By chance alone, some

>cases of SIDS can be expected to follow receipt of whole-cell pertussis DTP

>44 and DTaP. A review by a committee of the IOM concluded that available

>evidence did not indicate a causal relation between DTP vaccine and SIDS. 33

>

>Onset of infantile spasms has occurred in infants who have recently

>received DTP or DT. Analysis of data from the NCES on children with

>infantile spasms showed that receipt of DT or DTP was not causally related

>to infantile spasms. 45 The incidence of onset of infantile spasms

>increases at 3 to 9 months of age, the time period in which the second and

>third doses of DTP are generally given. Therefore, some cases of infantile

>spasms can be expected to be related by chance alone to recent receipt of

>DTP. 3

>

>A bulging fontanelle associated with increased intracranial pressure which

>occurred within 24 hours following DTP immunization has been reported,

>although a causal relationship has not been established. 33,46,47,48

>

>The above findings regarding possible association of unusual neurologic

>events and SIDS relate only to DTP vaccine containing whole-cell pertussis.

>At this time there are insufficient data to determine their relevance to

>Tripedia® vaccine.

>

>A review by the IOM found a causal relation between tetanus toxoid and

>brachial neuritis and Guillain-Barré syndrome. 40 The following illnesses

>have been reported as temporally associated with vaccine containing tetanus

>toxoid: neurological complications 49,50 including cochlear lesion, 51

>brachial plexus neuropathies, 51,52 paralysis of the radial nerve, 53

>paralysis of the recurrent nerve, 51 accommodation paresis, and EEG

>disturbances with encephalopathy. 17 In the differential diagnosis of

>polyradiculoneuropathies following administration of a vaccine containing

>tetanus toxoid, tetanus toxoid should be considered as a possible etiology.

>54,55

>

>In the German case-control study and US open-label safety study in which

>14,971 infants received Tripedia® vaccine, 13 deaths in Tripedia® vaccine

>recipients were reported to study investigators. Causes of deaths included,

>seven SIDS, and one of each of the following; enteritis, Leigh Syndrome,

>adrenogenital syndrome, cardiac arrest, motor vehicle accident and

>accidental drowning. None of these events were determined to be

>vaccine-related and all occurred more than two weeks past immunization. 1

>The rate of SIDS observed in the German case-control study was 0.4/1,000

>vaccinated infants. The rate of SIDS observed in the US open-label safety

>study was 0.8/1,000 vaccinated infants and the reported rate of SIDS in the

>US from 1985-1991 was 1.5/1,000 live births. 56 By chance alone, some cases

>of SIDS can be expected to follow receipt of whole-cell pertussis DTP 44

>and DTaP.

>

>In the Swedish efficacy trial where 1,419 recipients received the pertussis

>components in Tripedia® vaccine, three deaths due to invasive bacterial

>infections occurred. Further investigation revealed no evidence for a

>causal relation between vaccination and altered resistance to invasive

>disease caused by encapsulated bacteria. 11 While the hypothesis that the

>two variables are related cannot be ruled out in the Swedish trial, deaths

>due to invasive bacterial infections have been monitored in other trials.

>In contrast to the Swedish trial, in the German case-control study and US

>open-label safety study, 14,971 infants received Tripedia® vaccine and no

>deaths due to invasive bacterial infections were reported.

>

>When Tripedia® vaccine was used to reconstitute ActHIB® (TriHIBit®) and

>administered to children 15 to 20 months of age, the systemic adverse

>experience profile was comparable to that observed when the two vaccines

>were given separately. An increase in rates of minor local reactions was

>observed within the 24-hour period after immunization when compared to the

>Tripedia® and ActHIB® (OmniHIB®) vaccines administered separately. However,

>local adverse event rates of the combined vaccines were comparable when

>taking into consideration reactions observed at the ActHIB® site. 1 (Refer

>to ActHIB® package insert; Table 7.)

>

>

>

>Reporting of Adverse Events

>

>

>Reporting by parents and patients of all adverse events occurring after

>vaccine administration should be encouraged. Adverse events following

>immunization with vaccine should be reported by the health-care provider to

>the US Department of Health and Human Services (DHHS) Vaccine Adverse

>Events Reporting System (VAERS). Reporting forms and information about

>reporting requirements or completion of the form can be obtained from VAERS

>through a toll-free number 1-800-822-7967. 35,36,37

>

>The health-care provider also should report these events to the Director of

>Medical Affairs, Connaught Laboratories, Inc., a Pasteur Mérieux Connaught

>Company, Discovery Drive, Swiftwater, PA 18370-0187 or call 1-800-822-2463.

>

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>

>

>

>DOSAGE AND ADMINISTRATION

>

>

>Parenteral drug products should be inspected visually for extraneous

>particulate matter and/or discoloration prior to administration whenever

>solution and container permit. If these conditions exist, the vaccine

>should not be administered.

>

>SHAKE VIAL WELL before withdrawing each dose. Inject 0.5 mL of Tripedia®

>vaccine intramuscularly only. The preferred injection sites are the

>anterolateral aspect of the thigh and the deltoid muscle of the upper arm.

>The vaccine should not be injected into the gluteal area or areas where

>there may be a major nerve trunk.

>

>The primary series for children less than 7 years of age is three

>intramuscular doses of 0.5 mL. The customary age for the first dose is 2

>months of age but may be given as early as 6 weeks of age and up to the

>seventh birthday.

>

>Before injection, the skin over the site to be injected should be cleansed

>with a suitable germicide. After insertion of the needle, aspirate to

>ensure that the needle has not entered a blood vessel.

>

>Fractional doses (doses < 0.5 mL) should not be given. The effect of

>fractional doses on the frequency of serious adverse events and on efficacy

>has not been determined.

>

>Do NOT administer this product subcutaneously.

>

>

>

>

>

>PRIMARY IMMUNIZATION

>

>The primary series consists of three doses administered at intervals of 4

>to 8 weeks. It is recommended that Tripedia® vaccine be given for all three

>doses since no interchangeability data on DTaP vaccines exist for the

>primary series.

>

>Tripedia® vaccine may be used to complete the primary series in infants who

>have received one or two doses of whole-cell pertussis DTP. However, the

>safety and efficacy of Tripedia® vaccine in such infants has not been

>evaluated.

>

>Tripedia® vaccine should not be combined through reconstitution with any

>other vaccine for administration to infants younger than 15 months of age.

>There are insufficient data at this time to support the use of Tripedia®

>vaccine to reconstitute ActHIB® (TriHIBit®) for primary immunization.

>

>

>

>

>

>BOOSTER IMMUNIZATION

>

>When Tripedia® vaccine is given for the primary series, a fourth dose is

>recommended at 15 to 20 months of age. The interval between the third and

>fourth dose should be at least 6 months. At this time, data are

>insufficient to establish frequencies of adverse events following a fifth

>dose of Tripedia® vaccine in children who have previously received 4 doses

>of Tripedia® vaccine. (See

></nurse/static.htm?path=pdrel/pdr/62470460.htm#V05>ADVERSE REACTIONS

>section.)

>

>If a child receives whole-cell pertussis DTP for one or more doses,

>Tripedia® vaccine may be given to complete the five-dose series. A fourth

>dose is recommended at 15 to 20 months of age. The interval between the

>third and fourth dose should be at least 6 months. Children four to six

>years of age (up to the seventh birthday) who received all four doses by

>the fourth birthday, including one or more doses of whole-cell pertussis

>DTP, should receive a single dose of Tripedia® vaccine before entering

>kindergarten or elementary school. This dose is not needed if the fourth

>dose was given on or after the fourth birthday.

>

>Tripedia® vaccine combined with ActHIB® (TriHIBit®) by reconstitution, may

>be administered at 15 to 18 months of age for the fourth dose. (Refer to

>ActHIB® package insert.)

>

>Tripedia® vaccine may be administered according to any of the following

>schedules for infants and children 6 weeks through 6 years of age (up to

>the 7th birthday).

>

>

>

>

>

>

>

>

>Primary series

>

>* Three doses administered at intervals of 4 to 8 weeks, beginning at 6

>weeks of age

>* To complete the primary series for infants who have received one or two

>doses of DTP

>

>Booster doses

>

>* As a 4th and/or 5th dose following a primary series of three doses of DTP

>* As a 4th dose following a primary series of Tripedia® vaccine*

>* As a 4th dose when used to reconstitute ActHIB® (TriHIBit®)**

>

>

>

>

>

>

>

>*Data are insufficient to establish frequencies of adverse events following

>a fifth dose of Tripedia® vaccine in children who have previously received

>four doses of Tripedia® vaccine.

>

>**Tripedia® vaccine should not be combined through reconstitution with any

>other vaccine.

>

>If any recommended dose of pertussis vaccine cannot be given, DT (For

>Pediatric Use) should be given as needed to complete the series.

>

>PERSONS 7 YEARS OF AGE AND OLDER SHOULD NOT BE IMMUNIZED WITH TRIPEDIA®

>VACCINE. 28

>

>Preterm infants should be vaccinated according to their chronological age

>from birth. 20

>

>Interruption of the recommended schedule with a delay between doses should

>not interfere with the final immunity achieved with Tripedia® vaccine.

>There is no need to start the series over again, regardless of the time

>between doses.

>

>Routine simultaneous administration of DTaP, OPV (or IPV), Haemophilus b

>conjugate vaccine, MMR, and hepatitis B vaccine is encouraged for children

>who are the recommended age to receive these vaccines and for whom no

>specific contraindications exist at the time of the visit, unless, in the

>judgment of the provider, complete vaccination of the child will not be

>compromised by administering different vaccines at different visits.

>Simultaneous administration is particularly important if the child might

>not return for subsequent vaccinations (see

></nurse/static.htm?path=pdrel/pdr/62470460.htm#K05>CLINICAL PHARMACOLOGY

>section). 28

>

>Data are unavailable to the manufacturer concerning the effects on immune

>response of IPV when given concurrently with ActHIB® reconstituted with

>Tripedia® (TriHIBit®).

>

>If passive immunization is needed for tetanus prophylaxis, Tetanus Immune

>Globulin (Human) (TIG) is the product of choice. It provides longer

>protection than antitoxin of animal origin and causes few adverse

>reactions. The currently recommended prophylactic dose of TIG for wounds of

>average severity is 250 units intramuscularly. When tetanus toxoid and TIG

>are administered concurrently, separate syringes and separate sites should

>be used. The ACIP recommends the use of only adsorbed toxoid in this

>situation.

>

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>

>

>

>HOW SUPPLIED

>

>

>Vial, 1 Dose (5 per package) - Product No. 49281-288-05

>

>Vial, 15 Dose (7.5 mL) - Product No. 49281-288-15

>

>TriHIBit®, One 7.5 mL vial of Tripedia® vaccine as Diluent packaged with

>Ten 1 Dose vials of lyophilized ActHIB® - Product No. 49281-557-10

>

>TriHIBit®, Five 0.6 mL vials of Tripedia® vaccine as Diluent packaged with

>Five 1 Dose vials of lyophilized ActHIB® - Product No. 49281-557-05

>

>

>

>STORAGE

>

>

>Store between 2°-8°C (35°-46°F). DO NOT FREEZE. Temperature extremes may

>adversely affect resuspendability of this vaccine.

>

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>

>PRODUCT PHOTO(S):

>

>NOTE: These photos can be used only for identification by shape, color, and

>imprint. They do not depict actual or relative size.

>

>The product samples shown here have been supplied by the manufacturer and

>reproduced in full color by PDR as a quick-reference identification aid.

>While every effort has been made to assure accurate reproduction, please

>remember that any visual identification should be considered preliminary.

>In cases of poisoning or suspected overdosage, the drug's identity should

>be verified by chemical analysis.

>

>----------

>

>

>

>----------

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>

>

>

>

>

>REFERENCES

>

>

>

> * Unpublished data available from Connaught Laboratories, Inc.

>* Mueller JH, et al. Production of diphtheria toxin of high potency (100

>Lf) on a reproducible medium. J Immunol 40: 21-32, 1941

>* Recommendations of the Advisory Committee of Immunization Practices

>(ACIP). Diphtheria, Tetanus, and Pertussis: Recommendations for vaccine use

>and other preventive measures. MMWR 40: No RR-10, 1991

>* Kimura M, et al. Developments in pertussis immunisation in Japan. The

>Lancet: 30-32, 1990

>* Kimura M, et al. Current epidemiology of pertussis in Japan. Pediatr

>Infect Dis J 9: 705-709, 1990

>* Aoyama T, et al. Efficacy and immunogenicity of acellular pertussis

>vaccine by manufacturer and patient age. Amer J Dis Child 143: 655-659, 1989

>* Aoyama T, et al. Efficacy of an acellular pertussis vaccine in Japan. J

>Pediatr 107: 180-183, 1985

>* Blennow M, et al. Preliminary data from a clinical trial (phase 2) of an

>Acellular Pertussis Vaccine, J NIH-6. Develop Biol Standard 65: 185-190, 1986

>* Blennow M, et al. Primary immunization of infants with an Acellular

>Pertussis Vaccine in a double-blind randomized clinical trial. Pediatr 82:

>293-299, 1988

>* Kallings LO, et al. Placebo-controlled trial of two Acellular Pertussis

>Vaccines in Sweden - protective efficacy and adverse events. Lancet:

>955-960, 1988

>* Storsaeter J, et al. Mortality and morbidity from invasive bacterial

>infections during a clinical trial of acellular pertussis vaccines in

>Sweden. Pediatr Infect Dis J 7: 637-645, 1988

>* Bernstein H, et al. Clinical reactions and immunogenicity of the BIKEN

>Acellular Diphtheria and Tetanus Toxoids and Pertussis Vaccine in 4-

>through 6-year-old US children. Amer J Dis Child 146: 556-559, 1992

>* Feldman S, et al. Comparison of acellular (B-Type) and whole-cell

>pertussis-component diphtheria-tetanus-pertussis vaccines as the first

>booster immunization in 15- to 24-month old children. J Pediatr 121:

>857-861, 1992

>* Feldman S, et al. Comparison of two-component acellular and standard

>whole-cell pertussis vaccines, combined with diphtheria-tetanus toxoids, as

>the primary immunization series in infants. South Med J 86: 269-275, 284,

>1993

>* Pichichero ME, et al. Acellular pertussis vaccination of 2-month-old

>infants in the United States. J Pediatr 89: 882-887, 1992

>* CDC. Summary of Notifiable Disease, United States, 1994. MMWR 43: No. 53,

>1995

>* CDC. Diphtheria Epidemic - New Independent States of the Former Soviet

>Union, 1990-1994. MMWR 44: 177-181, 1995

>* Department of Health and Human Services, Food and Drug Administration.

>Biological Products; Bacterial Vaccines and Toxoids; Implementation of

>Efficacy Review; Proposed Rule. Federal Register Vol 50 No 240, pp

>51002-51117, 1985

>* CDC - Pertussis - United States, January 1992-June 1995. MMWR 44:

>525-529, 1995

>* Report of the Committee on Infectious Diseases. American Academy of

>Pediatrics, ton, Illinois. Twenty-third Edition, 1994

>* Farizo KM, et al. Epidemiologic features of pertussis in the United

>States, 1980-1989. Clin Infect Dis 14: 708-719, 1992

>* Nennig ME, et al. Prevalence and Incidence of Adult Pertussis in an Urban

>Population. JAMA (21) 275: 1672-1674, 1996

>* Linnemann CC, et al. Pertussis in the adult. Ann Rev Med 28: 179-185, 1977

>* CDC. Pertussis Surveillance - United States, 1986 and 1988. MMWR 39:

>57-66, 1990

>* Noble GR, et al. Acellular and whole-cell pertussis vaccines in Japan.

>JAMA 257: 1351-1356, 1987

>* Blackwelder WC, et al., Acellular Pertussis Vaccines. Efficacy and

>evaluation of clinical case definitions. Am J Dis Child: 145 (11):

>1285-1289, 1991

>* Olin P, et al. Relative efficacy of two acellular pertussis vaccines

>during three years of passive surveillance. Vaccine 10: pp 142-144, 1992

>* ACIP. General recommendations on immunization. MMWR 43: No. RR-1, 1994

>* GS. The Hazards of Immunization. Provocation poliomyelitis. pp

>270-274, 1967

>* ACIP. Pertussis Vaccination: Acellular Pertussis Vaccine for Reinforcing

>and Booster Use - Supplementary ACIP Statement. MMWR 41: No. RR-1, 1992

>* Cody CL, et al. Nature and rates of adverse reactions associated with DTP

>and DT immunizations in infants and children. Pediatr 68: 650-660, 1981

>* ACIP. Pertussis immunization: Family history of convulsions and use of

>antipyretics - Supplementary ACIP statement. MMWR 36: 281-282, 1987

>* Howson CP, et al. Adverse Effects of Pertussis and Rubella Vaccines,

>Pertussis Vaccines and CNS Disorders. Institute of Medicine (IOM). National

>Academy Press, Washington, DC, 1991

>* IOM. DTP vaccine and chronic nervous system dysfunction: a new analysis.

>National Academy Press, Washington, DC, 1994 (Supplement)

>* CDC. Vaccine Adverse Event Reporting System - United States. MMWR 39:

>730-733, 1990

>* CDC. National Childhood Vaccine Injury Act: requirements for permanent

>vaccination records and for reporting of selected events after vaccination.

>MMWR 37: 197-200, 1988

>* Food and Drug Administration. New reporting requirements for vaccine

>adverse events. FDA Drug Bull 18 (2), 16-18, 1988

>* Decker MD, et al. Comparison of 13 Acellular Pertussis Vaccines: Adverse

>Reactions. Pediatr 96: 557-566, 1995

>* Pichichero ME, et al. Safety and immunogenicity of an acellular pertussis

>vaccine booster in 15- to 20-month-old children previously immunized with

>acellular or whole-cell pertussis vaccine as infants. Pediatr 91: 756-760,

>1993

>* Stratton KR, et al. Adverse Events Associated with Childhood Vaccines.

>Evidence Bearing on Causality. IOM. National Academy Press. Washington, DC,

>1994

>* D, et al. Pertussis immunization and serious acute neurological

>illnesses in children. Academic Department of Public Health, St 's

>Hospital Medical School, University of London, 1993

>* MR, et al. Risk of sudden infant death syndrome after

>immunization with Diphtheria-Tetanus-Pertussis Vaccine. N Engl J Med

>618-623, 1988

>* Hoffman HJ, et al. Diphtheria-tetanus-pertussis immunization and sudden

>infant death: Results of the National Institute of Child Health and Human

>Development ative Epidemiological Study of Sudden Infant Death

>Syndrome Risk Factors. Pediatr 79: 598-611, 1987

>* AM, et al. Diphtheria-tetanus-pertussis immunization and sudden

>infant death syndrome. Am J Public Health 77: 945-951, 1987

>* Bellman MH, et al. Infantile spasms and pertussis immunization. Lancet,

>i: 1031-1034, 1983

>* J, et al. Increased intracranial pressure after diphtheria, tetanus

>and pertussis immunization. Am J Dis Child Vol 133: 217-218, 1979

>* Mathur R, et al. Bulging fontanel following triple vaccine. Indian

>Pediatr 18 (6): 417-418, 1981

>* Shendurnikar N, et al. Bulging fontanel following DTP vaccine. Indian

>Pediatr 23 (11): 960, 1986

>* Rutledge SL, et al. Neurological complications of immunizations. J

>Pediatr 109: 917-924, 1986

>* AM, et al. Neurologic events following

>diphtheria-tetanus-pertussis immunization. Pediatr 81: 345-349, 1988

>* GS. The Hazards of Immunization. Allergic manifestations:

>Post-vaccinal neuritis. pp 153-156, 1967

>* Tsairis P, et al. Natural history of brachial plexus neuropathy. Arch

>Neurol 27: 109-117, 1972

>* Blumstein GI, et al. Peripheral neuropathy following tetanus toxoid

>administration. JAMA 198: 1030-1031, 1966

>* CDC. Adverse events following immunization. Surveillance Report No. 3,

>1985-1986, Issued February 1989

>* Schlenska GK. Unusual neurological complications following tetanus toxoid

>administration. J Neurol 215: 299-302, 1977

>* Willinger M, et al. Infant Sleep Position and Risk for Sudden Infant

>Death Syndrome: Report of Meeting Held January 13 and 14, 1994, National

>Institutes of Health, Bethesda, MD. Pediatr 93: 814-819, 1994

>

>Product information as of September 1996

>

>Manufactured by:

>

>CONNAUGHT LABORATORIES, INC.

>

>Swiftwater, Pennsylvania 18370-0187, USA

>

>and

>

>The Research Foundation for Microbial

>

>Diseases of Osaka University ( " BIKEN® " )

>

>Suita, Osaka, Japan

>

>PASTEUR MERIEUX CONNAUGHT

>

>RHONE-POULENC GROUP

>

>3814/3819

>

>--------------------------------------------------------

>Sheri Nakken, R.N., MA

>Vaccination Information & Choice Network, Nevada City CA

>530-272-7306

>http://www.nccn.net/~wwithin/vaccine.htm

> " All that is necessary for the triumph of evil is that good men ( &

>women) do nothing " ...Edmund Burke

>

>ANY INFO OBTAINED HERE NOT TO BE CONSTRUED AS MEDICAL OR LEGAL ADVICE. THE

>DECISION TO VACCINATE IS YOURS AND YOURS ALONE.

>Well Within's Earth Mysteries & Sacred Site Tours

>http://www.nccn.net/~wwithin

>International Tours, Homestudy Courses, ANTHRAX & OTHER Vaccine Dangers

>Education, Homeopathic Education

>KVMR Broadcaster/Programmer/Investigative Reporter, Nevada City CA

>CEU's for nurses, Books & Multi-Pure Water Filters

>

>

>--------------------------------------------------------

>Sheri Nakken, R.N., MA

>Vaccination Information & Choice Network, Nevada City CA & Wales UK

>$$ Donations to help in the work - accepted by Paypal account

>vaccineinfo@...

>(go to http://www.paypal.com) or by mail

>PO Box 1563 Nevada City CA 95959 530-740-0561 Voicemail in US

>http://www.nccn.net/~wwithin/vaccine.htm

>ANY INFO OBTAINED HERE NOT TO BE CONSTRUED AS MEDICAL OR LEGAL ADVICE. THE

>DECISION TO VACCINATE IS YOURS AND YOURS ALONE.

>Well Within's Earth Mysteries & Sacred Site Tours

>http://www.nccn.net/~wwithin

>International Tours, Homestudy Courses, ANTHRAX & OTHER Vaccine Dangers

>Education, Homeopathic Education

>CEU's for nurses, Books & Multi-Pure Water Filters

>

>

>

>

>

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